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EXPERIMENTAL RESEARCH
Slc6a4 silencing alleviates ropivacaine-induced injury in myocardial infarction cell models
1
Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan City, Hubei Province, China
These authors had equal contribution to this work
Submission date: 2024-11-07
Final revision date: 2025-09-04
Acceptance date: 2025-10-09
Online publication date: 2026-01-20
Corresponding author
Jing Wan
Department of Anesthesiology The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology No. 26, Shengli Street Jiang’an District Wuhan City Hubei Province China, 430014
Department of Anesthesiology The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology No. 26, Shengli Street Jiang’an District Wuhan City Hubei Province China, 430014
Shenghua Li
Department of Anesthesiology The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology No. 26, Shengli Street Jiang’an District Wuhan City Hubei Province China, 430014
Department of Anesthesiology The Central Hospital of Wuhan Tongji Medical College Huazhong University of Science and Technology No. 26, Shengli Street Jiang’an District Wuhan City Hubei Province China, 430014
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Myocardial infarction (MI), often caused by atherosclerotic plaque rupture, leads to severe myocardial ischemia and necrosis. Despite advancements in treatment, its molecular mechanisms remain incompletely understood. Local anesthetics such as ropivacaine, while beneficial for pain control, may induce cardiotoxicity, complicating MI management. This study aimed to explore the effects of ropivacaine on H9c2 cardiomyocytes and the protective potential of Slc6a4 silencing against ropivacaine-induced cellular damage.
Material and methods:
Bioinformatics analysis of the GSE97320 dataset identified MI-associated differentially expressed genes (DEGs), which overlapped with ropivacaine-related genes. H9c2 cells were cultured and treated with ropivacaine to induce myocardial injury. The effects on cell cycle, apoptosis, and oxidative stress were assessed, and the role of Slc6a4 silencing under hypoxia/reoxygenation (H/R) conditions was investigated.
Results:
Ropivacaine induced G1 phase arrest and apoptosis in H9c2 cells, with increased Bax and caspase 3 levels and decreased Bcl-2. Oxidative stress was elevated, as evidenced by increased ROS, MDA, and LDH levels and reduced SOD, GSH, and ATP. Slc6a4 silencing under H/R conditions mitigated these effects, reducing cell cycle dysregulation and apoptosis by 40%, lowering NLRP3 inflammasome expression, and promoting Nrf2 nuclear translocation.
Conclusions:
This study demonstrates that Slc6a4 silencing alleviates ropivacaine-induced cellular damage by modulating oxidative stress, apoptosis, and cell cycle dynamics, suggesting a potential therapeutic strategy for myocardial ischemia-reperfusion injury.
Myocardial infarction (MI), often caused by atherosclerotic plaque rupture, leads to severe myocardial ischemia and necrosis. Despite advancements in treatment, its molecular mechanisms remain incompletely understood. Local anesthetics such as ropivacaine, while beneficial for pain control, may induce cardiotoxicity, complicating MI management. This study aimed to explore the effects of ropivacaine on H9c2 cardiomyocytes and the protective potential of Slc6a4 silencing against ropivacaine-induced cellular damage.
Material and methods:
Bioinformatics analysis of the GSE97320 dataset identified MI-associated differentially expressed genes (DEGs), which overlapped with ropivacaine-related genes. H9c2 cells were cultured and treated with ropivacaine to induce myocardial injury. The effects on cell cycle, apoptosis, and oxidative stress were assessed, and the role of Slc6a4 silencing under hypoxia/reoxygenation (H/R) conditions was investigated.
Results:
Ropivacaine induced G1 phase arrest and apoptosis in H9c2 cells, with increased Bax and caspase 3 levels and decreased Bcl-2. Oxidative stress was elevated, as evidenced by increased ROS, MDA, and LDH levels and reduced SOD, GSH, and ATP. Slc6a4 silencing under H/R conditions mitigated these effects, reducing cell cycle dysregulation and apoptosis by 40%, lowering NLRP3 inflammasome expression, and promoting Nrf2 nuclear translocation.
Conclusions:
This study demonstrates that Slc6a4 silencing alleviates ropivacaine-induced cellular damage by modulating oxidative stress, apoptosis, and cell cycle dynamics, suggesting a potential therapeutic strategy for myocardial ischemia-reperfusion injury.
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